Technologies that provide information on the single cell level may inevitably reveal specific mechanisms in a broad range of biological processes, from embryogenesis to aging. Most modern technologies study large populations of cells, with persistent heterogeneity of cells in different stages of growth or disease, yielding only an average measure of cellular function. However, studies at the single cell level are necessary to minimize inherent variability of measures from cell populations and enable detailed investigations for advanced cellular knowledge.
Information extracted from such studies is particularly useful when correlated with cell mechanics and adhesion properties. There are a variety of techniques that can elucidate these properties, for example, magnetic tweezers, optical tweezers, and atomic force microscopy (AFM). A comprehensive review illustrating the strengths and weaknesses of these techniques applied to single molecules is given by Neuman and Nagy. AFM provides a method of cellular stiffness measurement, in a non-destructive way by applying nanoscale forces to a cell. As opposed to traditional optical imaging, AFM indirectly visualizes the cell surface morphology via monitoring the deflection of a sensing cantilever. AFM can further acquire stretching curves, through the pressing of the cantilever on the surface and determining the subsequent adhesion during the tip retraction. A distinct advantage of this technology is that other techniques such as brightfield, confocal, and fluorescence microscopy can be incorporated to enable cellular shape and labeling of proteins on the cell interior.
Nuclear magnetic resonance (NMR) imaging was introduced in 1973 and has since become a primary diagnostic tool in medical science for internal tissue morphology, disease, and function. To reveal microstructures and sub microstructures of objects, considerable efforts have been made to improve the resolution of NMR microscopy to depict elements smaller than 100 cubic microns (μm3). However, the practical constraints imposed by modern imaging systems are currently thought to limit spatial resolution to about 1.0 microns (μm) and volume elements to less than 64 μm3. Moreover, reported spatial resolutions for cellular imaging are rather poor, around 3 μm, and the acquisition times are long (i.e., approximately 8 hours).
Accordingly, there is a need for a device and method that enables the analysis of cellular structures and local biochemistry to speed innovative basic research toward treatments and cures of cellular disease. Such a device and method would provide a foundation for the analysis of local biomechanical and chemical environments of single cells in the context of disease, potentially enabling the success of embedded individual cells used for regeneration of functional tissue engineered constructs.